The present invention relates generally to a novel class of polymeric compounds which are useful as antimicrobials in pharmaceutical and cosmetic compositions. In particular, the present invention relates to novel polymeric compounds having spacer moieties in between amine and/or ammonium moieties. The compounds of the present invention are useful as disinfectants and preservatives for pharmaceutical products, including ophthalmic compositions and contact lens care products.
It is well known that small organic compounds, such as benzalkonium chloride (BAC), chlorhexidine, thimerosal have excellent antimicrobial activity. These compounds have been commercially used as preservatives and disinfectants for many years; however, there are some significant disadvantages to using these compounds, especially in ophthalmic and contact lens compositions. In particular, it is now known that these small organic antimicrobials are often toxic to the sensitive tissues of the eye and can accumulate in contact lenses, particularly soft, hydrophilic contact lenses. Accumulation of these antimicrobial compounds in contact lenses may cause eye irritation, and leaching of such compounds may occur while the lens is in the eye, causing further irritation and possibly damaging the cornea.
Several classes of polymeric antimicrobials were subsequently developed to overcome the disadvantages of the above-described monomeric compounds. These polymeric antimicrobials had lower cytotoxicity and had minimal interaction with biomaterials. Such antimicrobials include those described in U.S. Pat. No. 3,931,319 (Jan. 6, 1976), U.S. Pat. No. 4,001,432 (Jan. 4, 1977) and U.S. Pat. No. 4,012,446 (Mar. 15, 1977), all issued to Green, et al. and U.S. Pat. No. 4,836,986 (Jun. 6, 1989), issued to Ogunbiyi. Although these polymeric antimicrobials exhibit a broad spectrum of antimicrobial activity, including activity against Candida albicans and Pseudononas aeruginosa, the above-described polymeric antimicrobials generally have relatively weak antifungal activity, especially against Aspergillus niger and Aspergillus fumigates.
Second generation polymeric antimicrobials have since been developed, including those described in the following publications: WO 91/09522 (Wong et al.) and WO 91/09523 (Dziabo et al.). The antimicrobials disclosed in Wong et al. are quaternary ammonium-substituted matrix materials, wherein the matrix material is selected from proteinaceous materials, carbohydrate materials or mixtures thereof. Dziabo et al. disclose certain quaternary ammonium polymers which are useful as ophthalmic antimicrobials.